The present invention relates to a method of mass spectrometry and a mass spectrometer.
Mass spectrometers configured for Matrix Assisted Laser Desorption Ionisation (“MALDI”) are known. MALDI is a soft ionisation technique for mass spectrometry in which analyte molecules are prepared on the surface of a target plate. The analyte molecules are supported in a solid polycrystalline matrix. A pulse of laser radiation, with a typical duration of a few nanoseconds, is directed onto the MALDI sample. The laser radiation is strongly absorbed by the matrix molecules.
The pulse of laser energy results in rapid heating of the region that is irradiated. This heat causes a proportion of the matrix material to be vaporised and explosively ejected from the surface as a plume of gaseous material (desorption). Analyte ions embedded within the matrix that is desorbed are transferred to the gaseous phase along with the matrix.
Reactions between the matrix ions and the analyte molecules can result in the analyte molecules being ionised either through protonation/deprotonation or through the removal or addition of an ion. Upon dispersal of the initial MALDI plume, the remaining analyte ions are predominantly singly charged.
Although the absorption of the laser radiation occurs at all levels of laser fluence, there is a threshold energy density required in order to obtain desorption of material under illumination.
MALDI imaging is a growing technique where the sample to be analysed may be a thin (typically 15 μm) section of tissue, with a layer of matrix deposited upon the surface of the sample. The sample is scanned in a raster manner, with the laser firing at specific locations or ranges of locations spaced along the raster pattern. Mass spectra are acquired at each location or range of locations and the relative abundance of ion masses are then displayed as an ion image of the tissue section.
Large matrix arrays can be generated to cover entire tissue sections (i.e. ion imaging) or smaller arrays can be used to study different areas within the tissue (e.g. depth profiling).
The aim of depth profiling is to obtain information on the variation of composition with depth below the initial surface of the sample. The information which is obtained is particularly useful for the analysis of layered structures such as those produced in the semiconductor industry.
Laser Desorption Ionisation relies upon the removal of ions from the surface of a sample and hence is, by its nature, a destructive technique. Laser Desorption Ionisation may be used for depth profiling applications. A depth profile of a sample may be obtained by recording sequentially spectra as the surface is gradually eroded away by the incident laser beam probe. A plot of the intensity of a given mass or mass to charge ratio signal as a function of time may be produced which is a direct reflection of the variation of its abundance or concentration with depth below the surface.
MALDI tissue profiling and ion imaging techniques have become valuable tools for rapid, direct analysis of tissues to investigate spatial distributions of proteins.
However, the production of mass spectra relating to each of the different areas within a tissue sample requires discrete analyses which is time consuming and reduces instrument yield.
US 2005/0116158 (University of Manitoba) discloses an ion transmission device or interface between a pulsed ion source and a mass spectrometer. The ion transmission device comprises a multipole rod set and includes a damping gas to damp spatial and energy spreads of ions generated by the pulsed ion source. The disclosed arrangement attempts to homogenise ions emitted by the pulsed ion source into a quasi-continuous beam. Broadening the pulse increases the probability of a pusher region of a Time of Flight mass analyser having ions present in the pusher region at the time when the electrodes forming the pusher region are energised. If the packets of ions were still of a size comparable to the time of ion formation (i.e. approx. 3 ns laser pulse duration) then the probability of ions being in the pusher region would be relatively low.
It is known to address this problem in a different manner by timing and synchronising the release of ion packets from a device with energisation of the pusher electrodes. As a result, ions can always be arranged to be present in the pusher region at the precise time when the pusher electrodes are energised. This results in a High Duty Cycle (“HDC”) mode of operation.
Operating a mass spectrometer in a HDC mode in conjunction with a travelling wave ion mobility spectrometer enables ions within a desired mass range of interest to be present in the pusher region when the pusher electrodes are energised. As a result, there is no need to broaden the pulses of ions to ensure that the ions are sampled. The delay time between releasing ion packets and the timing of energising the pusher electrode may be calibrated for the expected mass range of ions emerging from e.g. the ion mobility spectrometer.
It is desired to provide an improved method of mass spectrometry and an improved mass spectrometer.